Laboratory of Precision NanoMedicine, Shmunis School for Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
Theranostics. 2023 Jun 12;13(11):3497-3508. doi: 10.7150/thno.82228. eCollection 2023.
: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery. We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model. : We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice. We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy.
: 在过去的十年中,癌症治疗取得了显著的进展,提供了新的策略来抑制癌细胞生长,包括免疫调节,以及基因治疗。具体来说,自杀基因疗法和免疫毒素已被研究用于通过直接癌细胞细胞毒性治疗肿瘤。最近在 mRNA 递送上的进展也证明了基于 mRNA 的疫苗和免疫调节剂在癌症治疗中的潜力,利用纳米载体进行 mRNA 递送。我们设计了一种细菌毒素编码的修饰 mRNA,通过脂质纳米粒递送到 B16-黑色素瘤小鼠模型中。我们表明,局部给予包裹修饰 mRNA 的 LNPs,该 mRNA 编码细菌毒素,可诱导显著的抗肿瘤作用,并提高治疗小鼠的总生存率。我们提出了负载 mmRNA 的 LNPs 作为一种新型的基于毒素的抗肿瘤治疗方法。